Synthesis and evaluation of oryzalin analogs against Toxoplasmagondii

The synthesis and evaluation of 20 dinitroanilines and related compounds against the obligate intracellular parasite Toxoplasmagondii is reported. Using in vitro cultures of parasites in human fibroblasts, we determined that most of these compounds selectively disrupted Toxoplasma microtubules, and several displayed sub-micromolar potency against the parasite. The most potent compound was N1,N1-dipropyl-2,6-dinitro-4-(trifluoromethyl)-1,3-benzenediamine (18b), which displayed an IC50 value of 36 nM against intracellular T. gondii. Based on these data and another recent report [Ma, C.; Tran, J.; Gu, F.; Ochoa, R.; Li, C.; Sept, D.; Werbovetz, K.; Morrissette, N. Antimicrob. AgentsChemother. 2010, 54, 1453], an antimitotic structure–activity relationship for dinitroanilines versus Toxoplasma is presented.

Figure optionsDownload as PowerPoint slide